The Cochrane 2018 Review on Brief Interventions in Primary Care for Hazardous and Harmful Alcohol Consumption: A Distillation for Clinicians and Policy Makers.

AIMS: An updated Cochrane systematic review assessed effectiveness of screening and brief intervention to reduce hazardous or harmful alcohol consumption in general practice or emergency care settings. This paper summarises the implications of the review for clinicians. METHODS: Cochrane methods were followed. Reporting accords with PRISMA guidance. We searched multiple resources to September 2017, seeking randomised controlled trials of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. Brief intervention was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 min. Our primary outcome was alcohol consumption, measured as or convertible to grams per week. We conducted meta-analyses to assess change in consumption, and subgroup analyses to explore the impact of participant and intervention characteristics. RESULTS: We included 69 studies, of which 42 were added for this update. Most studies (88%) compared brief intervention to control. The primary meta-analysis included 34 studies and provided moderate-quality evidence that brief intervention reduced consumption compared to control after one year (mean difference -20 g/wk, 95% confidence interval -28 to -12). Subgroup analysis showed a similar effect for men and women. CONCLUSIONS: Brief interventions can reduce harmful and hazardous alcohol consumption in men and women. Short, advice-based interventions may be as effective as extended, counselling-based interventions for patients with harmful levels of alcohol use who are presenting for the first time in a primary care setting.

High prevalence of alcohol use disorders in patients with inflammatory skin diseases.

BACKGROUND: There is a known association between psoriasis and heavy alcohol consumption. The association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined. OBJECTIVES: To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease. METHODS: We conducted an observational cross-sectional study in a single hospital outpatient department. We recruited 609 patients with either psoriasis, eczema, cutaneous lupus or other inflammatory disorders, and a reference population with skin lesions. Primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD). RESULTS: The observed prevalence of AUD was 30·6% in patients with psoriasis, 33·3% in those with eczema, 12·3% in those with cutaneous lupus, 21·8% in those with other inflammatory disease and 14·3% in those with non-inflammatory disease. Odds ratios (OR) for AUD in patients in the inflammatory groups compared with those in the noninflammatory groups, adjusted for age and sex, were as follows: psoriasis 1·65 [95% confidence interval (CI) 0·86-3·17], eczema 2·00 (95% CI 1·03-3·85), lupus 1·03 (95% CI 0·39-2·71), other inflammatory disease 1·32 (95% CI 0·68-2·56). ORs were reduced if also adjusted for Dermatology Life Quality Index (DLQI). The prevalence of DLQI ≥ 11 was 31·1% for psoriasis, 43·7% for eczema, 17·5% for cutaneous lupus, 17·2% for other inflammatory disease and 2·8% for noninflammatory disease. CONCLUSIONS: Patients with eczema attending a hospital clinic have been shown to have high levels of AUD of a similar level to patients with psoriasis and higher than patients with noninflammatory skin diseases.

Association between an anti-inflammatory and anti-oxidant dietary pattern and diabetes in British adults: results from the national diet and nutrition survey rolling programme years 1-4.

This study investigated the cross-sectional association between an anti-inflammatory and anti-oxidant dietary pattern and diabetes in the national diet and nutrition survey (NDNS) rolling programme years 1-4. A total of 1531 survey members provided dietary data. Reduced Rank Regression (RRR) was used to derive an anti-inflammatory and anti-oxidant dietary pattern. Serum C-reactive protein (CRP) and plasma carotenoids were selected as response variables and markers of inflammation and antioxidant status, respectively. Overall, 52 survey members had diabetes. The derived anti-inflammatory and anti-oxidant dietary pattern was inversely related to CRP and positively to carotenoids. It was associated with lower odds of diabetes (multivariate adjusted OR for highest compared with lowest quintile: 0.17; 95%CI: 0.04-0.73; p for linear trend = 0.013). In conclusion, an anti-inflammatory and anti-oxidant dietary pattern is inversely related to diabetes. Further research is required to understand the overall framework within which foods and nutrients interact to affect metabolic pathways related to diabetes risk.

ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

Risks from ionising radiation: an HPA viewpoint paper for Safegrounds.

Safegrounds is a forum for developing and disseminating good practice guidance on the management of radioactively contaminated land on nuclear and defence sites in the UK. This review has been provided to Safegrounds as a summary of the basis for current radiation risk estimates and the International Commission on Radiological Protection (ICRP) protection system, in a form that will be accessible to a wide range of stakeholders. Safegrounds has also received viewpoint papers from other members who contend that the ICRP methodology results in substantial underestimates of risk, particularly for internal emitters. There is an extensive literature on the risks of radiation exposure, regularly reviewed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and other expert groups. These data provide a sound basis for the system of protection recommended by ICRP. The available epidemiological and experimental evidence supports the application of cancer risk estimates derived for acute, high dose, external exposures to low dose exposures to external and internal sources. In the context of radioactively contaminated land on nuclear and defence sites, the national standards for the cleaning up of land and for waste disposal correspond to very low doses, two orders of magnitude less than average annual doses in the UK from natural background radiation (10-20  µSv compared with 2-3 mSv). Risks at such very low doses can only be estimated on the basis of observations after exposure of population groups at much higher doses. The estimated risks at these very low doses, while uncertain, are as likely to be overestimates as underestimates.

Cerebrovascular diseases in the cohort of workers first employed at Mayak PA in 1948-1958.

The incidence of and mortality from cerebrovascular diseases (CVD) have been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2000. Information on external γ-ray doses is available for virtually all of these workers (99.9%); the mean total γ-ray dose (± SD) was 0.91 ± 0.95 Gy (99th percentile 3.9 Gy) for men and 0.65 ± 0.75 Gy (99th percentile 2.99 Gy) for women. In contrast, plutonium body burden was measured only for 30.0% of workers; among those monitored, the mean cumulative liver dose from plutonium α-particle exposure (± SD) was 0.40 ± 1.15 Gy (99th percentile 5.88 Gy) for men and 0.81 ± 4.60 Gy (99th percentile 15.95 Gy) for women. A total of 4418 cases of CVD, including 665 cases of stroke, and 753 deaths from CVD, including 404 deaths from stroke, were identified in the study cohort. Having adjusted for non-radiation factors, there were statistically significant increasing trends in CVD incidence but not mortality with both total external γ-ray dose and internal liver dose. Much of the evidence for increased incidence in relation to external dose arose for workers with cumulative doses above 1 Gy. Although the dose response is consistent with linearity, the statistical power to detect non-linearity at external doses below 1 Gy was low. CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy. There was a statistically significant increasing trend in incidence with increasing internal dose, even after adjusting for external dose, although the trend estimates differed between workers at different plants. The risk estimates for external radiation are generally compatible with those from other large occupational studies, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.

Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948-1958.

Incidence of and mortality from cardiovascular diseases have been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2000. Information on external gamma-ray doses is available for virtually all of these workers (99.9%); the mean total gamma-ray dose (+/-SD) was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. In contrast, plutonium body burden was measured for only 30.0% of workers; among those monitored, the mean cumulative liver dose from plutonium alpha exposure (+/- SD) was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women. A total of 3751 cases of ischemic heart disease (IHD), including 683 cases of acute myocardial infarction (AMI), and 1495 IHD deaths, including 338 AMI deaths, were identified in the study cohort during the follow-up period. Having adjusted for non-radiation factors, there were statistically significant increasing trends with both total external gamma-ray dose and internal liver dose in IHD incidence. The trend with internal dose was weaker and was not statistically significant after adjusting for external dose, whereas the external dose trend was little changed after adjusting for internal dose. The trend with external dose in IHD mortality was not statistically significantly greater than zero but was consistent with the corresponding trend in IHD incidence. The estimated trend in IHD mortality with internal dose was lower and was not statistically significant once adjustment was made for external dose. There was a statistically significantly increasing trend in AMI incidence but not AMI incidence with external dose. The risk estimates for IHD in relation to external radiation are generally compatible with those from other large occupational studies and the Japanese A-bomb survivors.

Radiation cataractogenesis: a review of recent studies.

The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and it is known that cataracts can be induced by acute doses of less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of protracted radiation. Although much work has been carried out in this area, the exact mechanisms of radiation cataractogenesis are still not fully understood. In particular, the question of the threshold dose for cataract development is not resolved. Cataracts have been classified as a deterministic effect of radiation exposure with a threshold of approximately 2 Gy. Here we review the combined results of recent mechanistic and human studies regarding induction of cataracts by ionizing radiation. These studies indicate that the threshold for cataract development is certainly less than was previously estimated, of the order of 0.5 Gy, or that radiation cataractogenesis may in fact be more accurately described by a linear, no-threshold model.

Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers.

Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a 'healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2-3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.

Cancer in the offspring of female radiation workers: a record linkage study.

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child's conception may be at an increased risk of childhood cancer. An additional 16,964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52,612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.

Studies of occupational radiation exposure and health: experience from the UK National Registry for Radiation Workers.

Studies of persons exposed to radiation in the course of their work are directly relevant to the task of estimating the health risks of protracted radiation exposures. However, such investigations are not always easy to undertake, and not all studies are equally informative. Considerable care is required, therefore, in order to be able to draw reliable inferences from studies of radiation workers. This paper highlights some important aspects concerning the design, conduct and interpretation of such investigations, with reference to experience gained from a large long-term study of radiation workers in the United Kingdom (the National Registry for Radiation Workers, NRRW). Key findings from the NRRW are summarised, together with a brief description of a recent international study and of work in progress.

New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report.

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

What are the risks from medical X-rays and other low dose radiation?

The magnitude of the risks from low doses of radiation is one of the central questions in radiological protection. It is particularly relevant when discussing the justification and optimization of diagnostic medical exposures. Medical X-rays can undoubtedly confer substantial benefits in the healthcare of patients, but not without exposing them to effective doses ranging from a few microsieverts to a few tens of millisieverts. Do we have any evidence that these levels of exposure result in significant health risks to patients? The current consensus held by national and international radiological protection organizations is that, for these comparatively low doses, the most appropriate risk model is one in which the risk of radiation-induced cancer and hereditary disease is assumed to increase linearly with increasing radiation dose, with no threshold (the so-called linear no threshold (LNT) model). However, the LNT hypothesis has been challenged both by those who believe that low doses of radiation are more damaging than the hypothesis predicts and by those who believe that they are less harmful, and possibly even beneficial (often referred to as hormesis). This article reviews the evidence for and against both the LNT hypothesis and hormesis, and explains why the general scientific consensus is currently in favour of the LNT model as the most appropriate dose-response relationship for radiation protection purposes at low doses. Finally, the impact of the LNT model on the assessment of the risks from medical X-rays and how this affects the justification and optimization of such exposures is discussed.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.